The proposed studies are directed toward the underlying mechanism leading to the formation of cholesterol gallstones in man. As a correlary to these studies information will also be obtained on the regulation of cholesterol in hyperlipemias. Studies will be carried out on two important aspects of cholesterol metabolism in man a) the nature of bile acid pathways with particular emphasis on the intermediates from 5 Beta-cholestane 3 Alpha, 7 Alpha diol to 5 Beta-cholestane 3 Alpha, 7 Alpha, 26 triol, b) the characterization and nature of the multicompartmental hepatic and plasma cholesterol system. Specifically, it is planned to administer a series of labeled 5 Beta-cholesterol intermediates (3 Alpha, 7 Alpha diol, 3 Alpha, 7 Alpha, 26 triol, etc.) to patients with T-tubes and isolate labeled products and intermediates in normal and cirrhotic patients. Information will be obtained on the nature of products found and the efficiency of conversion to primary bile acids. The compartment studies will be carried out in T-tube and normal patients given labeled mevalonic acid and labeled cholesterol. Emphasis will be placed on further validation of the model and application to the aberrations in cholesterol metabolism (gallstones, hyperlipemias). BIBLIOGRAPHIC REFERENCES: Swell, L., Schwartz, C.C., Halloran, L. Gregg, and Vlahcevic, Z.R.: Rapid feedback inhibition of endogenous cholic and chenodeoxycholic acid synthesis by exogenous chenodeoxycholic acid in man. Biochem. Biophys. Res. Comm. 64:1083-1089, 1975. Schwartz, C.C., Vlahcevic, A.R., Halloran, L.G., Gregory, D.H., Meek, J.B., and Swell, L.: Evidence for the existence of definitive hepatic cholesterol precursor compartments for bile acids and biliary cholesterol in man. Gastroenterology 69:1379-1382, 1975.